Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study

Merenäkk, Liis; Mäestu, Jarek; Nordquist, Niklas; Parik, Jüri; Oreland, Lars; Loit, Helle‐Mai; Harro, Jaanus

doi:10.1007/s00213-010-2109-z

Cited by 31 publications

(18 citation statements)

References 73 publications

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“…However, there was also evidence for two direct effects. Those with the 5-HTTLPR SS genotype had higher rates of problematic alcohol use, which maps on to prior work with youth (Merenäkk et al, 2011). Mesolimbic serotonergic pathways have been demonstrated to play a critical role in the development of alcohol dependence and ethanol tolerance (Türker et al, 1998).…”

Section: Discussionmentioning

confidence: 60%

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Trucco

Hicks

Villafuerte

et al. 2016

Journal of Abnormal Psychology

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Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent non-specific neurobiological underpinnings for an externalizing pathway to addiction.

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Section: Discussionmentioning

confidence: 60%

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Trucco

Hicks

Villafuerte

et al. 2016

Journal of Abnormal Psychology

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“…This gene encodes alpha2A subtype and it contains no introns in either its coding or untranslated sequences. There is an extensive literature on the gene and many findings suggesting association to ADHD (e.g., Kim et al, 2010; Roman et al, 2005; Roman et al, 2003; Waldman et al, 2006), as well as metabolic traits (e.g., glycemic phenotypes, blood pressure) (for meta-analysis see Talmud et al, 2011) and substance abuse (Clarke et al, 2012; Merenakk et al, 2011; Prestes et al, 2007). Given the neurobiological implications, this gene should be considered a strong candidate in future alcohol abuse studies.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood

et al. 2015

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The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse and dependence increasing across adolescence and peaking in early adulthood. Here we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three, longitudinal community samples (N=2,126, obs=12,166). Consumption repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and 6 others met our “suggestive” criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms including neurotransmission, xenobiotic pharmacodynamics and nuclear hormone receptors. These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.

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“…Experimental manipulation of serotonergic levels in an animal study [12] showed that decreasing serotonergic functioning increased alcohol intake. Human observational studies, however, have yielded inconsistent results concerning the association of the 5-HTTLPR genotype with adolescent alcohol use [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 95%

Interaction effects between the 5‐hydroxy tryptamine transporter‐linked polymorphic region (5‐HTTLPR) genotype and family conflict on adolescent alcohol use and misuse

et al. 2014

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Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study

Abstract: Our results reveal that expression of genetic vulnerability for substance use in children and adolescents may depend on age, gender, interaction of genes, and type of substance.

Cited by 31 publications

References 73 publications

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use.

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood

Interaction effects between the 5‐hydroxy tryptamine transporter‐linked polymorphic region (5‐HTTLPR) genotype and family conflict on adolescent alcohol use and misuse

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